Breast cancer is the most common form of cancer in women. An increasing emphasis on early detection, along with more effective treatments, has resulted in increased survival rates. While it is recognized that chemotherapy can cause cognitive impairment, often termed "chemobrain", most of the studies done to date have limitations and few have focused on underlying brain mechanisms. We propose to use neuroimaging, both MRI and PET, along with cognitive testing to evaluate the acute and relatively long-term effects of chemotherapy on brain structure and function in breast cancer patients. Our long-term goal is to establish a cohort of breast cancer patients in which to longitudinally evaluate chronic effects of chemotherapy on imaging measures and cognitive function. Three groups of breast cancer patients will be studied: a group that will receive chemotherapy plus hormonal therapy, and a group that will be treated with hormonal therapy only, and a group that will receive chemotherapy only. We will also study a group of healthy women as control group. All subjects will receive a baseline PET scan, MRI and cognitive testing. The chemotherapy groups will receive additional scans and cognitive testing at one and 18 months post- treatment to evaluate both acute and relatively long-term effects of chemotherapy. The other groups will also be scanned and tested at the same intervals. We hypothesize that the patients who receive chemotherapy will show reductions in cerebral glucose metabolism that may be global or regional. MRI will be used to explore both cortical and subcortical structural changes, such as hippocampal volume, whole brain volume, and white matter hyperintensities (WMH). Previous studies suggest that we may see increased WMH patients who receive chemotherapy. We expect to see both acute and long-term cognitive deficits in the chemotherapy groups, involving multiple cognitive domains. The proposed studies may help to define the mechanisms of cognitive impairment following treatment for breast cancer. This project is relevant to public health because identifying the mechanisms of cognitive impairment may lead to different treatment strategies that do not negatively impact cognitive function. They are also relevant to the overall mission of the NIH because of the negative impact that cognitive dysfunction has on quality of life. [unreadable] [unreadable] [unreadable]